9-Deoxy-9-methylene-PGF1 -piperizinylamides

ABSTRACT

The present invention relates to novel 9-deoxy-9-methylene-PGF 1  -piperizinylamides. These compounds are useful pharmacological agents, and are useful for the same purposes as the corresponding 9-deoxy-9-methylene-PGF-type acids.

This application is a continuation-in-part of Ser. No. 786,250, filed Apr. 11, 1977, now U.S. Pat. No. 4,098,805, issued July 4, 1978.

The present invention relates to novel 9-deoxy-9-methylene-PGF₁ -piperizinylamides, the essential material constituting a disclosure of which is incorporated here by reference from U.S. Pat. No. 4,098,805. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein Y₁ is trans--CH═CH--, --C.tbd.C--, or --CH₂ CH₂ --wherein M₁ is ##STR2## wherein R₅ is hydrogen or methyl; WHEREIN L₁ is ##STR3## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;Wherein Z₂ is (1) --(CH₂)₃ --(CH₂)_(g) --CH₂ --, (2) --(ch₂)₃ --(ch₂)_(g) --CF₂ --, (3) --ch₂ --o--ch₂ --(ch₂)_(g) --CH₂ --, (4) --c.tbd.c--ch₂ --(ch₂)_(g) --CH₂ --, (5) --ch₂ --c.tbd.c--(ch₂)_(g) --CH₂ --, ##STR4## WHEREIN G IS ONE, 2 OR 3; WHEREIN R₇ is (1) --(CH₂)_(m) --CH₃, ##STR5## WHEREIN M IS ONE TO 5, INCLUSIVE, H IS ZERO OR ONE, T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl, with the further proviso that R₇ is ##STR6## WHEREIN T and s are as defined above, only when R₃ and R₄ are hydrogen or methyl, being the same or different; and wherein R₂₁ and R₂₂ are hydrogen, alkyl of one to 12 carbon atoms, inclusive; aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, 2, or 3 chloro or alkyl of one to 3 carbon atoms, inclusive, or phenyl substituted with hydroxycarbonyl or alkoxycarbonyl of one to 4 carbon atoms, inclusive.
 2. A prostaglandin analog according to claim 1, wherein Y₁ is --C.tbd.C--.
 3. 9-Deoxy-9-methylene-13,14-didehydro-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 2. 4. A prostaglandin analog according to claim 1, wherein Y₁ is --CH₂ CH₂ --.
 5. 9-Deoxy-9-methylene-13,14-dihydro-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 4. 6. A prostaglandin analog according to claim 1, wherein Y₁ is trans--CH.tbd.CH--.
 7. A prostaglandin analog according to claim 6, wherein Z₂ is aromatic.
 8. 9-Deoxy-9-methylene-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 7. 9. 9-Deoxy-9-methylene-3,7-inter-m-phenylene-4,5,6-trinor-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 7. 10. A prostaglandin analog according to claim 6, wherein Z₂ is aliphatic.
 11. A prostaglandin analog according to claim 10, wherein M₁ is ##STR7##
 12. 15-epi-9-deoxy-9-methylene-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 11. 13. A prostaglandin analog according to claim 10, wherein M₁ is ##STR8##
 14. A prostaglandin analog according to claim 13, wherein Z₂ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 15. A prostaglandin analog according to claim 14, wherein R₇ is ##STR9##
 16. 9-Deoxy-9-methylene-17-phenyl-18,19,20-trinor-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 15. 17. A prostaglandin analog according to claim 14, wherein R₇ is ##STR10##
 18. 9-Deoxy-9-methylene-16-phenoxy-17,18,19,20-tetranor-PGF₁, piperizinylamide, a prostaglanding analog according to claim
 17. 19. A prostaglandin analog according to claim 14, wherein R₇ is --(CH₂)_(m) --CH₃.
 20. A prostaglandin analog according to claim 19, wherein m is
 3. 21. A prostaglandin analog according to claim 20, wherein g is
 3. 22. 2a,2b-Dihomo-9-deoxy-9-methylene-15-methyl-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 21. 23. A prostaglandin analog according to claim 20, wherein g is one.
 24. A prostaglandin analog according to claim 23, wherein at least one of R₃ and R₄ is methyl.
 25. 9-Deoxy-9-methylene-16,16-dimethyl-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 24. 26. A prostaglandin analog according to claim 23, wherein at least one of R₃ and R₄ is fluoro.
 27. 9-Deoxy-9-methylene-16,16-difluoro-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 26. 28. A prostaglandin analog according to claim 23, wherein R₃ and R₄ are both hydrogen.
 29. A prostaglandin analog according to claim 28, wherein R₅ is methyl.
 30. 9-Deoxy-9-methylene-15-methyl-PGF₁, piperizinylamide, a prostaglandin analog according to claim
 29. 31. A prostaglandin analog according to claim 28, wherein R₅ is hydrogen.
 32. 9-Deoxy-9-methylene-PFG₁, piperizinylamide, a prostaglandin analog according to claim
 31. 